Platelet-activating factor antagonist, BN-52021 protects against cis-diamminedichloroplatinum nephrotoxicity in the rat.
The protective effect of the platelet-activating factor (PAF) antagonist, BN 52021, was assessed on cis-diammine-dichloroplatinum (CDDP)-induced nephrotoxicity. Wistar male rats were treated with either a single dose of CDDP (10 mg/kg b.w. ip) alone or in association with 7 daily doses of BN 52021 (10 mg/kg b.w. ip). At the end of the experiment, the CDDP-treated rats lost 25% of body weight and serum creatinine and urea increased from 0.041 +/- 0.006 mmol/l and 0.165 +/- 0.007 g/l for the control group to 0.202 +/- 0.019 mmol/l and 1.51 +/- 0.131 g/l versus CDDP respectively. Body weight, serum creatinine, serum urea and creatinine clearances were similar to the control group in animals treated with CDDP and BN 52021. CDDP caused proximal tubular necrosis and dilatation of cortical collecting tubes, changes that were markedly less in the BN 52021-protected animals. The concomitant administration of BN 52021 with CDDP did not modify the plasma pharmacokinetic of CDDP. In addition, BN 52021 did not interfere with the antiproliferative and antitumoral actions of CDDP in cultured human tumor cells. BN 52021 therefore could prevent the nephrotoxicity of CDDP.
Pirotzky
E
E
Institut Henri Beaufour Research Labs., Les Ulis, France.
Guilmard
C
C
Sidoti
C
C
Ivanow
F
F
Principe
P
P
Braquet
P
P
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000503:physiopathology; D000818:Animals; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D002945:Cisplatin / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics / Q000633:toxicity; D003404:Creatinine / Q000378:metabolism; D004224:Diterpenes; D046934:Ginkgolides; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D003404:Creatinine; C045856:ginkgolide B; D002945:Cisplatin